Short communicationEffects of nematode infection on sensitivity to intestinal distension: Role of tachykinin NK2 receptors
Introduction
In anaesthetised rats, distension of the gastrointestinal tract causes a cardiovascular depressor response which is considered to be predictive of visceral nociception (Ness and Gebhart, 1990). To date, knowledge of the pharmacology of this reflex is somewhat limited. 5-HT3 receptors have been shown to be involved (Moss and Sanger, 1990) and the reflex is abolished in capsaicin-treated rats (Lembeck and Skofitsch, 1982). Therefore, the purpose of the current study was to extend this knowledge via an investigation into the involvement of tachykinins, specifically tachykinin NK2 receptors. The involvement of tachykinins was chosen for investigation since they have been implicated in the transmission of somatic nociception (e.g. Seguin et al., 1995) acting via tachykinin NK1 and NK2 receptors. Tachykinin NK1 and NK2 receptors have also been implicated in visceral nociception (Julia et al., 1994).
The study also aimed to investigate whether the post-inflammatory, neuroimmune changes, that persist in rats previously infected with Nippostrongylus (N.) brasiliensis (Stead, 1992) affect sensitivity to intestinal distension and if so to determine whether this hypersensitivity is limited to the areas of hypermastocytosis or extended to other unaffected regions. The possible involvement of tachykinin NK2 receptors in the hypersensitivity was also investigated.
Section snippets
Surgical and experimental procedure
Control or post-N. brasiliensis-infected (30 days post-infection) male Wistar rats (330–400 g) were used. Infection was achieved via subcutaneous injection of 5000 third stage infective larvae of N. brasiliensis in 0.5 ml sterile saline inoculated into the flank of the rats. Rats were anaesthetised with pentobarbitone sodium (60 mg/kg, s.c.). The trachea was cannulated and mean systemic blood pressure was recorded via the left common carotid artery.
Jejunal (7 cm from the ligament of Treitz) or
Histological and myeloperoxidase analysis
Inflammatory sites were not detected macroscopically or microscopically in intestinal tissue samples from control (n=9) and post-infected rats (n=9). However, significant hypermastocytosis was observed in the jejunum (control, 73±30 mast cells/mm2 tissue, n=9; post-infected, 317±109 mast cells/mm2 tissue, n=9; P<0.05) but not in the colon (control, 82±52 mast cells/mm2 tissue, n=9; post-infected, 129±63 mast cells/mm2 tissue; P>0.05) in post-infected rats.
Myeloperoxidase activity values were
Discussion
This study has shown that the chronic changes which occur in rat jejunum post-infection with N. brasiliensis, at a time when intestinal inflammation, as assessed by myeloperoxidase activity, has resolved cause increased sensitivity to distension an effect which was limited to the areas of hypermastocytosis. The data obtained with SR48968 show, for the first time, that tachykinin NK2 receptor antagonists, inhibit nociception in response to noxious jejunal distension in anaesthetised rats, an
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